The goals of this project are to study factors controlling the proliferation and differentiation of hematopoietic stem cells and neutrophilic granulocytes. A major emphasis is to study granulocyte progenitor cells (CFU-C) in the in vitro culture system. In the presence of colony stimulating factor (OSF), CFU-C from blood or marrow proliferate to form colonies of granulocytes and macrophages. Human studies are designed to understand and characterize kinetic changes in various forms of neutropenia and to determine if quantitative and/or qualitative abnormalities in progenitor cells are present in these disorders. Lithium induced neutrophilia will be studied to determine its effect on CFU-C, CFU-S, and various blood and marrow granulocyte pools. In other studies, viral induced leukopenia and neutropenia will be studied in order to understand the mechanism underlying the neutropenia. The role of activated complement (C) components on neutrophil production and kinetics will be studied in animals with complement activated in vivo and in vitro. Factors affecting the proliferation and differentiation of stem cells (CFU-S) and committed progenitor cells will be studied in the Dexter long term continuous culture system. Other studies will include identifyingand characterizing a population of spleen cells which suppress granulocyte proliferation in the soft gel culture system.